tbuckley/cabot-search huggingface dataset:
Type 2 immunity in the brain and brain borders
Authors: Tornike Mamuladze, Jonathan Kipnis
Journal: Cellular and Molecular Immunology (2023)

Abstract Recent research in neuroimmunology has revolutionized our understanding of the intricate interactions between the immune system and the central nervous system (CNS). The CNS, an “immune-privileged organ”, is now known to be intimately connected to the immune system through different cell types and cytokines. While type 2 immune responses have traditionally been associated with allergy and parasitic infections, emerging evidence suggests that these responses also play a crucial role in CNS homeostasis and disease pathogenesis. Type 2 immunity encompasses a delicate interplay among stroma, Th2 cells, innate lymphoid type 2 cells (ILC2s), mast cells, basophils, and the cytokines interleukin (IL)-4, IL-5, IL-13, IL-25, TSLP and IL-33. In this review, we discuss the beneficial and detrimental roles of type 2 immune cells and cytokines in CNS injury and homeostasis, cognition, and diseases such as tumors, Alzheimer’s disease and multiple sclerosis.
Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller
Authors: Luis M. Molinos-Albert, Eduard Baquero, Mélanie Bouvin-Pley, Valérie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valérie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Véronique Avettand-Fenoël, Asier Sáez-Cirión, Hugo Mouquet
Journal: Cell Host & Microbe (2023)
Heart failure-induced cognitive dysfunction is mediated by intracellular Ca2+ leak through ryanodine receptor type 2
Authors: Haikel Dridi, Yang Liu, Steven Reiken, Xiaoping Liu, Elentina K. Argyrousi, Qi Yuan, Marco C. Miotto, Leah Sittenfeld, Andrei Meddar, Rajesh Kumar Soni, Ottavio Arancio, Alain Lacampagne, Andrew R. Marks
Journal: Nature Neuroscience (2023)

Abstract Cognitive dysfunction (CD) in heart failure (HF) adversely affects treatment compliance and quality of life. Although ryanodine receptor type 2 (RyR2) has been linked to cardiac muscle dysfunction, its role in CD in HF remains unclear. Here, we show in hippocampal neurons from individuals and mice with HF that the RyR2/intracellular Ca 2+ release channels were subjected to post-translational modification (PTM) and were leaky. RyR2 PTM included protein kinase A phosphorylation, oxidation, nitrosylation and depletion of the stabilizing subunit calstabin2. RyR2 PTM was caused by hyper-adrenergic signaling and activation of the transforming growth factor-beta pathway. HF mice treated with a RyR2 stabilizer drug (S107), beta blocker (propranolol) or transforming growth factor-beta inhibitor (SD-208), or genetically engineered mice resistant to RyR2 Ca 2+ leak (RyR2-p.Ser2808Ala), were protected against HF-induced CD. Taken together, we propose that HF is a systemic illness driven by intracellular Ca 2+ leak that includes cardiogenic dementia.
Positron emission tomography and magnetic resonance imaging methods and datasets within the Dominantly Inherited Alzheimer Network (DIAN)
Authors: Nicole S. McKay, Brian A. Gordon, Russ C. Hornbeck, Aylin Dincer, Shaney Flores, Sarah J. Keefe, Nelly Joseph-Mathurin, Clifford R. Jack, Robert Koeppe, Peter R. Millar, Beau M. Ances, Charles D. Chen, Alisha Daniels, Diana A. Hobbs, Kelley Jackson, Deborah Koudelis, Parinaz Massoumzadeh, Austin McCullough, Michael L. Nickels, Farzaneh Rahmani, Laura Swisher, Qing Wang, Ricardo F. Allegri, Sarah B. Berman, Adam M. Brickman, William S. Brooks, David M. Cash, Jasmeer P. Chhatwal, Gregory S. Day, Martin R. Farlow, Christian la Fougère, Nick C. Fox, Michael Fulham, Bernardino Ghetti, Neill Graff-Radford, Takeshi Ikeuchi, William Klunk, Jae-Hong Lee, Johannes Levin, Ralph Martins, Colin L. Masters, Jonathan McConathy, Hiroshi Mori, James M. Noble, Gerald Reischl, Christopher Rowe, Stephen Salloway, Raquel Sanchez-Valle, Peter R. Schofield, Hiroyuki Shimada, Mikio Shoji, Yi Su, Kazushi Suzuki, Jonathan Vöglein, Igor Yakushev, Carlos Cruchaga, Jason Hassenstab, Celeste Karch, Eric McDade, Richard J. Perrin, Chengjie Xiong, John C. Morris, Randall J. Bateman, Tammie L. S. Benzinger, Adam. M. Brickman, Christian la Fougère
Journal: Nature Neuroscience (2023)

Abstract The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case–control studies. The age of onset in ADAD is highly predictable within families, allowing researchers to estimate an individual’s point in the disease trajectory. These characteristics allow candidate AD biomarker measurements to be reliably mapped during the preclinical phase. Although ADAD represents a small proportion of AD cases, understanding neuroimaging-based changes that occur during the preclinical period may provide insight into early disease stages of ‘sporadic’ AD also. Additionally, this study provides rich data for research in healthy aging through inclusion of the non-carrier controls. Here we introduce the neuroimaging dataset collected and describe how this resource can be used by a range of researchers.
Specialized Networks for Social Cognition in the Primate Brain
Authors: Ben Deen, Caspar M. Schwiedrzik, Julia Sliwa, Winrich A. Freiwald
Journal: Annual Review of Neuroscience (2023)

Primates have evolved diverse cognitive capabilities to navigate their complex social world. To understand how the brain implements critical social cognitive abilities, we describe functional specialization in the domains of face processing, social interaction understanding, and mental state attribution. Systems for face processing are specialized from the level of single cells to populations of neurons within brain regions to hierarchically organized networks that extract and represent abstract social information. Such functional specialization is not confined to the sensorimotor periphery but appears to be a pervasive theme of primate brain organization all the way to the apex regions of cortical hierarchies. Circuits processing social information are juxtaposed with parallel systems involved in processing nonsocial information, suggesting common computations applied to different domains. The emerging picture of the neural basis of social cognition is a set of distinct but interacting subnetworks involved in component processes such as face perception and social reasoning, traversing large parts of the primate brain.
Neural Networks for Navigation: From Connections to Computations
Authors: Rachel I. Wilson
Journal: Annual Review of Neuroscience (2023)

Many animals can navigate toward a goal they cannot see based on an internal representation of that goal in the brain's spatial maps. These maps are organized around networks with stable fixed-point dynamics (attractors), anchored to landmarks, and reciprocally connected to motor control. This review summarizes recent progress in understanding these networks, focusing on studies in arthropods. One factor driving recent progress is the availability of the Drosophila connectome; however, it is increasingly clear that navigation depends on ongoing synaptic plasticity in these networks. Functional synapses appear to be continually reselected from the set of anatomical potential synapses based on the interaction of Hebbian learning rules, sensory feedback, attractor dynamics, and neuromodulation. This can explain how the brain's maps of space are rapidly updated; it may also explain how the brain can initialize goals as stable fixed points for navigation.
How coupled slow oscillations, spindles and ripples coordinate neuronal processing and communication during human sleep
Authors: Bernhard P. Staresina, Johannes Niediek, Valeri Borger, Rainer Surges, Florian Mormann
Journal: Nature Neuroscience (2023)

Abstract Learning and plasticity rely on fine-tuned regulation of neuronal circuits during offline periods. An unresolved puzzle is how the sleeping brain, in the absence of external stimulation or conscious effort, coordinates neuronal firing rates (FRs) and communication within and across circuits to support synaptic and systems consolidation. Using intracranial electroencephalography combined with multiunit activity recordings from the human hippocampus and surrounding medial temporal lobe (MTL) areas, we show that, governed by slow oscillation (SO) up-states, sleep spindles set a timeframe for ripples to occur. This sequential coupling leads to a stepwise increase in (1) neuronal FRs, (2) short-latency cross-correlations among local neuronal assemblies and (3) cross-regional MTL interactions. Triggered by SOs and spindles, ripples thus establish optimal conditions for spike-timing-dependent plasticity and systems consolidation. These results unveil how the sequential coupling of specific sleep rhythms orchestrates neuronal processing and communication during human sleep.
Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts
Authors: Siri H. Strand, Belén Rivero-Gutiérrez, Kathleen E. Houlahan, Jose A. Seoane, Lorraine M. King, Tyler Risom, Lunden A. Simpson, Sujay Vennam, Aziz Khan, Luis Cisneros, Timothy Hardman, Bryan Harmon, Fergus Couch, Kristalyn Gallagher, Mark Kilgore, Shi We, Angela DeMichele, Tari King, Priscilla F. McAuliffe, Julie Nangia, Joanna Lee, Jennifer Tseng, Anna Maria Storniolo, Alastair M. Thompson, Gaorav P. Gupta, Robyn Burns, Deborah J. Veis, Katherine DeSchryver, Chunfang Zhu, Magdalena Matusiak, Jason Wang, Shirley X. Zhu, Jen Tappenden, Daisy Yi Ding, Dadong Zhang, Jingqin Luo, Shu Jiang, Sushama Varma, Lauren Anderson, Cody Straub, Sucheta Srivastava, Christina Curtis, Rob Tibshirani, Robert Michael Angelo, Allison Hall, Kouros Owzar, Kornelia Polyak, Carlo Maley, Jeffrey R. Marks, Graham A. Colditz, E. Shelley Hwang, Robert B. West
Journal: Cancer Cell (2023)

(Cancer Cell 40, 1521–1536.e1–e7; December 12, 2022) In the originally published version of this paper, some errors were introduced during the final preparation of Table 1. First, for the RAHBT cohort, the values for “Lumpectomy + radiation” and “Lumpectomy – radiation” were transposed. Second, in the RAHBT “DCIS with invasive recurrence” group, the number of samples with grade 3 DCIS should be n = 3, not 2 as listed. Third, for the RAHBT “DCIS without recurrence” group, there should be n = 53 ER+, not 55 as listed; and n = 15 ER−, not 13 as listed. Table 1 has been corrected in the original article online. The authors apologize for any confusion these errors might have caused. Since these errors only occurred in Table 1, none of the analyses or the conclusions of the paper are affected. Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohortsStrand et al.Cancer CellNovember 17, 2022In BriefStrand et al. have performed a large, comprehensive study to generate a spatially resolved breast precancer atlas. They present a prognostic classifier that predicts both precancer recurrence and invasive progression, which may form the basis for a future clinical test to guide breast precancer treatment. Full-Text PDF Open Access
Cholesterol Metabolism in Aging and Age-Related Disorders
Authors: Gesine Saher
Journal: Annual Review of Neuroscience (2023)

All mammalian cell membranes contain cholesterol to maintain membrane integrity. The transport of this hydrophobic lipid is mediated by lipoproteins. Cholesterol is especially enriched in the brain, particularly in synaptic and myelin membranes. Aging involves changes in sterol metabolism in peripheral organs and also in the brain. Some of those alterations have the potential to promote or to counteract the development of neurodegenerative diseases during aging. Here, we summarize the current knowledge of general principles of sterol metabolism in humans and mice, the most widely used model organism in biomedical research. We discuss changes in sterol metabolism that occur in the aged brain and highlight recent developments in cell type-specific cholesterol metabolism in the fast-growing research field of aging and age-related diseases, focusing on Alzheimer's disease. We propose that cell type-specific cholesterol handling and the interplay between cell types critically influence age-related disease processes.
MAPK-negative feedback regulation confers dependence to JAK2V617F signaling
Authors: Meenu Kesarwani, Zachary Kincaid, Mohammad Azhar, Jacob Menke, Joshua Schwieterman, Sekhu Ansari, Angela Reaves, Michael E. Deininger, Ross Levine, H. Leighton Grimes, Mohammad Azam
Journal: Leukemia (2023)
Heat-related mortality in Europe during the summer of 2022
Authors: Joan Ballester, Marcos Quijal-Zamorano, Raúl Fernando Méndez Turrubiates, Ferran Pegenaute, François R Herrmann, Jean Marie Robine, Xavier Basagaña, Cathryn Tonne, Josep M Antó, Hicham Achebak
Journal: Nature Medicine (2023)

Abstract Over 70,000 excess deaths occurred in Europe during the summer of 2003. The resulting societal awareness led to the design and implementation of adaptation strategies to protect at-risk populations. We aimed to quantify heat-related mortality burden during the summer of 2022, the hottest season on record in Europe. We analyzed the Eurostat mortality database, which includes 45,184,044 counts of death from 823 contiguous regions in 35 European countries, representing the whole population of over 543 million people. We estimated 61,672 (95% confidence interval (CI) = 37,643–86,807) heat-related deaths in Europe between 30 May and 4 September 2022. Italy (18,010 deaths; 95% CI = 13,793–22,225), Spain (11,324; 95% CI = 7,908–14,880) and Germany (8,173; 95% CI = 5,374–11,018) had the highest summer heat-related mortality numbers, while Italy (295 deaths per million, 95% CI = 226–364), Greece (280, 95% CI = 201–355), Spain (237, 95% CI = 166–312) and Portugal (211, 95% CI = 162–255) had the highest heat-related mortality rates. Relative to population, we estimated 56% more heat-related deaths in women than men, with higher rates in men aged 0–64 (+41%) and 65–79 (+14%) years, and in women aged 80+ years (+27%). Our results call for a reevaluation and strengthening of existing heat surveillance platforms, prevention plans and long-term adaptation strategies.
Targeting the TCA cycle can ameliorate widespread axonal energy deficiency in neuroinflammatory lesions
Authors: Yi-Heng Tai, Daniel Engels, Giuseppe Locatelli, Ioanna Emmanouilidis, Caroline Fecher, Delphine Theodorou, Stephan A. Müller, Simon Licht-Mayer, Mario Kreutzfeldt, Ingrid Wagner, Natalia Prudente de Mello, Sofia-Natsouko Gkotzamani, Laura Trovò, Arek Kendirli, Almir Aljović, Michael O. Breckwoldt, Ronald Naumann, Florence M. Bareyre, Fabiana Perocchi, Don Mahad, Doron Merkler, Stefan F. Lichtenthaler, Martin Kerschensteiner, Thomas Misgeld
Journal: Nature Metabolism (2023)

Inflammation in the central nervous system can impair the function of neuronal mitochondria and contributes to axon degeneration in the common neuroinflammatory disease multiple sclerosis (MS). Here we combine cell-type-specific mitochondrial proteomics with in vivo biosensor imaging to dissect how inflammation alters the molecular composition and functional capacity of neuronal mitochondria. We show that neuroinflammatory lesions in the mouse spinal cord cause widespread and persisting axonal ATP deficiency, which precedes mitochondrial oxidation and calcium overload. This axonal energy deficiency is associated with impaired electron transport chain function, but also an upstream imbalance of tricarboxylic acid (TCA) cycle enzymes, with several, including key rate-limiting, enzymes being depleted in neuronal mitochondria in experimental models and in MS lesions. Notably, viral overexpression of individual TCA enzymes can ameliorate the axonal energy deficits in neuroinflammatory lesions, suggesting that TCA cycle dysfunction in MS may be amendable to therapy.
Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results
Authors: Martin Gutierrez, Wei-Sen Lam, Matthew D. Hellmann, Matthew A. Gubens, Charu Aggarwal, Daniel Shao Weng Tan, Enriqueta Felip, Joanne W. Y. Chiu, Jong-Seok Lee, James Chih-Hsin Yang, Edward B. Garon, Giovanna Finocchiaro, Myung-Ju Ahn, Alexander Luft, Gregory A. Landers, Andrea Basso, Hua Ma, Julie Kobie, John Palcza, Razvan Cristescu, Lawrence Fong, Alexandra Snyder, Jianda Yuan, Roy S. Herbst
Journal: Nature Medicine (2023)
How Flies See Motion
Authors: Alexander Borst, Lukas N. Groschner
Journal: Annual Review of Neuroscience (2023)

How neurons detect the direction of motion is a prime example of neural computation: Motion vision is found in the visual systems of virtually all sighted animals, it is important for survival, and it requires interesting computations with well-defined linear and nonlinear processing steps—yet the whole process is of moderate complexity. The genetic methods available in the fruit fly Drosophila and the charting of a connectome of its visual system have led to rapid progress and unprecedented detail in our understanding of how neurons compute the direction of motion in this organism. The picture that emerged incorporates not only the identity, morphology, and synaptic connectivity of each neuron involved but also its neurotransmitters, its receptors, and their subcellular localization. Together with the neurons’ membrane potential responses to visual stimulation, this information provides the basis for a biophysically realistic model of the circuit that computes the direction of visual motion.
Pathologic complete response in advanced non-small-cell lung cancer following preoperative chemotherapy: implications for the design of future non-small-cell lung cancer combined modality trials.
Authors: K M Pisters, M G Kris, R J Gralla, M B Zaman, R T Heelan, N Martini
Journal: Journal of Clinical Oncology (1993)

PURPOSE This report determines the incidence of pathologic complete response in patients with locally advanced non-small-cell lung cancer (NSCLC) treated with mitomycin, vinca alkaloid, and high-dose cisplatin (MVP) chemotherapy, and estimates the effect of MVP on survival. PATIENTS AND METHODS We have identified and reviewed the course of 21 patients with advanced NSCLC who achieved a pathologic complete response following a median of three preoperative MVP combination chemotherapy courses including vinblastine or vindesine, cisplatin (120 mg/m2), and mitomycin (n = 19). RESULTS All patients had a major objective response following preoperative chemotherapy and nine (43%) had a clinical complete response. Nine patients with pathologic complete responses were among 73 entered on a preoperative chemotherapy program, yielding an incidence estimate of 12% (95% confidence interval, 6% to 22%). The median survival duration for all 21 patients has not been reached. The median follow-up duration is now 68 months (range, 17 to 109). Survival estimates are 90% at 1 year, 62% at 3 years, and 54% at 5 years. Nine patients have relapsed with initial sites of recurrence as follows: brain (n = 5), other systemic sites (n = 3), and locoregional (n = 1). One patient died in the postoperative period. Eleven patients remain disease-free and all have excellent functional status. CONCLUSION We have observed pathologic complete responses in approximately 12% of advanced NSCLC patients treated with preoperative MVP chemotherapy. These pathologically determined responses were seen only in patients with major objective responses clinically. Pathologic complete response predicts excellent survival and functional level and should be considered a major end point in the evaluation of preoperative chemotherapy programs.
RNA polymerase II dynamics shape enhancer–promoter interactions
Authors: Gilad Barshad, James J. Lewis, Alexandra G. Chivu, Abderhman Abuhashem, Nils Krietenstein, Edward J. Rice, Yitian Ma, Zhong Wang, Oliver J. Rando, Anna-Katerina Hadjantonakis, Charles G. Danko
Journal: Nature Genetics (2023)
Ribonucleicacid interference or small molecule inhibition of <i>Runx</i>1 in the border zone prevents cardiac contractile dysfunction following myocardial infarction
Authors: Tamara P Martin, Eilidh A MacDonald, Ashley Bradley, Holly Watson, Priyanka Saxena, Eva A Rog-Zielinska, Anmar Raheem, Simon Fisher, Ali Ali Mohamed Elbassioni, Ohood Almuzaini, Catriona Booth, Morna Campbell, Alexandra Riddell, Pawel Herzyk, Karen Blyth, Colin Nixon, Lorena Zentilin, Colin Berry, Thomas Braun, Mauro Giacca, Martin W McBride, Stuart A Nicklin, Ewan R Cameron, Christopher M Loughrey
Journal: Cardiovascular Research (2023)

Abstract Aims Myocardial infarction (MI) is a major cause of death worldwide. Effective treatments are required to improve recovery of cardiac function following MI, with the aim of improving patient outcomes and preventing progression to heart failure. The perfused but hypocontractile region bordering an infarct is functionally distinct from the remote surviving myocardium and is a determinant of adverse remodelling and cardiac contractility. Expression of the transcription factor RUNX1 is increased in the border zone 1-day after MI, suggesting potential for targeted therapeutic intervention. Objective This study sought to investigate whether an increase in RUNX1 in the border zone can be therapeutically targeted to preserve contractility following MI. Methods and results In this work we demonstrate that Runx1 drives reductions in cardiomyocyte contractility, calcium handling, mitochondrial density, and expression of genes important for oxidative phosphorylation. Both tamoxifen-inducible Runx1-deficient and essential co-factor common β subunit (Cbfβ)-deficient cardiomyocyte-specific mouse models demonstrated that antagonizing RUNX1 function preserves the expression of genes important for oxidative phosphorylation following MI. Antagonizing RUNX1 expression via short-hairpin RNA interference preserved contractile function following MI. Equivalent effects were obtained with a small molecule inhibitor (Ro5-3335) that reduces RUNX1 function by blocking its interaction with CBFβ. Conclusions Our results confirm the translational potential of RUNX1 as a novel therapeutic target in MI, with wider opportunities for use across a range of cardiac diseases where RUNX1 drives adverse cardiac remodelling.